226 1. lODOACETATE AND lODOACETAMIDE 



creased with a rise in temperature, it was postulated that iodoacetate might 

 block this response by its known action on the EM pathway. 



Stomach smooth muscle fails quite rapidly in the presence of 1 mM iodo- 

 acetate, usually after about 20 contractions when it is spontaneously ac- 

 tive, and then passes into rigor (Schmitt, 1935). If the muscle is stimulated 

 electrically, the same sequence occurs but faster. If sufficient iodoacetate is 

 administered to a frog to affect the skeletal muscles, there is little obvious 

 effect on the stomach muscle, but if the muscle is removed it can be readily 

 shown to be definitely altered. It is also known that iodoacetate causes a 

 fall in ATP in the rabbit stomach (Lange, 1955). 



Uterus 



The guinea pig uterus is stimulated by low concentrations (0.72 mM) of 

 bromoacetate, but passes into rigor at higher concentrations (7.2 mM) 

 (Neuss, 1931). Iodoacetate at 1 mM causes a maximal contraction, which 

 is followed by a jmralysis during which the uterus cannot be stimulated by 

 various basic substances normally effective (Klingenberg and Lipp, 1961). 

 The activity of pregnant rat uterus is abolished by 0.2 mM iodoacetate 

 irreversibly and the action potential is reduced, but there is no evidence of 

 depolarization; the response to oxytocin is also lost (Marshall and Miller, 

 1964). The respiration of rat and rabbit uteri is inhibited 50% by 0.7 mM 

 and 2 mM iodoacetate, respectively (Graubard, 1941). It is evident that 

 we have little knowledge of the effects of iodoacetate on the uterus, but 

 there is no reason for believing it departs markedly from the behavior of 

 other muscles. 



Blood Vessels 



The results obtained on vascular smooth muscle are conflicting and diffi- 

 cult to interpret. Some workers have found only constriction, for example 

 in the frog or guinea pig during perfusion (Neuss, 1931) or the cat hind 

 limbs (Hitchcock, 1946), rather high concentrations (1-7.2 mM) being used. 

 On the other hand, perfusion of the rabbit ear or guinea pig hind limbs 

 with iodoacetate at concentrations above 1.1 mM produces only dilatation 

 and edema, according to Dobrowolski (1933). Issekutz et al. (1951 a, b) have 

 made the only thorough study of this problem. They perfused the femoral 

 artery of dogs and observed a marked dilatation (blood flow rose from 

 17-18 to 80-85 ml/min), which was partially reversible, and vasoconstric- 

 tion eventually occurred. There is some difficulty in deciding whether these 

 changes arise from effects on the vessels directly or are secondary to meta- 

 bolic alterations in the muscles. Cyanide normally causes vasodilatation, but 

 after iodoacetate it fails to do so and may constrict. A similar effect was 

 noted on the responses to acetylcholine and epinephrine, both of which 

 normally dilate the vessels but after iodoacetate produce more and more 



